Primary Hyperoxaluria: Developing a Clinic Protocol

Introduction: Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder resulting in a deficiency in the hepatic enzyme alanine-glyoxylate aminotransferase. This leads to an inability to metabolize glyoxylate, leading to high levels of oxalate in the blood and urine, which causes oxalate nephropathy and can form calcium oxalate stones. Inherited in an autosomal recessive pattern, PH1 typically presents in childhood. Here, we follow two siblings. Patient A is a 22 year old male, presenting with eGFR 18, requiring initiation of hemodialysis. And Patient B is a healthy 25 year old female, with normal creatinine and eGFR >90. Case Description: Both patients were diagnosed with PH1 by genetic testing. At their first clinic appointment, they were started on pyridoxine, and calcium carbonate; instructed to increase water intake to 2-3 L/day; and referral was made to nutrition services for counseling on low oxalate diet. Start form for lumasiran was initiated, which required documentation of genetic testing, recent chart notes, lab results, and letter of medical necessity. Additionally, documentation of increased urinary oxalate excretion or plasma oxalate levels were required. Monitoring includes plasma oxalate vs urine oxalate creatinine ratio vs 24 hour urine oxalate excretion; as well as eGFR by CKD-EPI-R and eGFR by Cystatin C. Discussion: This experience has led to the development of a more efficient protocol for management of oxalate nephropathy, referral for lumasiran, and monitoring of patients with hyperoxaluria vs hemodialysis dependent patients. Additionally, two patients have been identified in the practice with oxalate nephropathy with no genetic explanation. One patient developed in the post transplant period, and the other perhaps due to dietary factors. As we explore this further, questions arise about epigenetics, fad diets, medications, use of gadolinium, and other factors. Is it possible to monitor liver enzyme levels, or is there a role for liver biopsy? Is there a role for more genetic testing and stone risk assessment for transplant donors and recipients? Is there an application for lumasiran in patients outside of AGTX mutation PH1?